Germ cell apoptosis: relevance to infertility and contraception

Abstract

Spermatogenesis is a dynamic process in which stem spermatogonia through a series of events become mature spermatozoa. Not all germ cells achieve maturity and cell death by apoptosis appears to be a constant feature of normal spermatogenesis in a variety of mammalian species to maintain proper germ cell numbers. It is because of the obvious importance of the germ cells in the context of species propagation, the testis has very active prosurvival and proapoptotic systems that together regulate the extent of germ cell apoptosis. A growing body of evidence demonstrates that both spontaneous and increased germ cell death are triggered by various regulatory stimuli, including deprivation of gonadotropins and intratesticular testosterone by gonadotropin-releasing hormone antagonist or by estradiol or testosterone treatment, exposure to local testicular heating, toxicants, and chemotherapeutic agents. This review focuses on the cell death events that occur in testis under various conditions and provide an assessment of the knowledgebase existing on the role of pro and anti-apoptotic proteins and involvement of the cell death receptor and the mitochondrial pathway during germ cell apoptosis. Various knockout or mutant models of pro and anti-apoptotic proteins are discussed with an aim to provide an overview of requirement of various genes in germ cell apoptosis.